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1. Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis

Author

Kamper, Jorg, Kahmann, Regine, Bolker, Michael, Ma, Li-Jun, Brefort, Thomas, Saville, Barry J., Banuett, Flora, Kronstad, James W., Gold, Scott E., Muller, Olaf, Perlin, Michael H., Wosten, Han A. B., de Vries, Ronald, Ruiz-Herrera, Jose, Reynaga-Pena, Cristina G., Snetselaar, Karen, McCann, Michael, Perez-Martin, Jose, Feldbrugge, Michael, Basse, Christoph W., Steinberg, Gero, Ibeas, Jose I., Holloman, William, Guzman, Plinio, Farman, Mark, Stajich, Jason E., Sentandreu, Rafael, Gonzalez-Prieto, Juan M., Kennell, John C., Molina, Lazaro, Schirawski, Jan, Mendoza-Mendoza, Artemio, Greilinger, Doris, Munch, Karin, Rossel, Nicole, Scherer, Mario, Vraneš, Miroslav, Ladendorf, Oliver, Vincon, Volker, Fuchs, Uta, Sandrock, Bjorn, Meng, Shaowu, Ho, Eric C. H., Cahill, Matt J., Boyce, Kylie J., Klose, Jana, Klosterman, Steven J., Deelstra, Heine J., Ortiz-Castellanos, Lucila, Li, Weixi, Sanchez-Alonso, Patricia, Schreier, Peter H., Hauser-Hahn, Isolde, Vaupel, Martin, Koopmann, Edda, Friedrich, Gabi, Voss, Hartmut, Schluter, Thomas, Margolis, Jonathan, Platt, Darren, Swimmer, Candace, Gnirke, Andreas, Chen, Feng, Vysotskaia, Valentina, Mannhaupt, Gertrud, Guldener, Ulrich, Munsterkotter, Martin, Haase, Dirk, Oesterheld, Matthias, Mewes, Hans-Werner, Mauceli, Evan W., DeCaprio, David, Wade, Claire M., Butler, Jonathan, Young, Sarah, Jaffe, David B., Calvo, Sarah, Nusbaum, Chad, Galagan, James, and Birren, Bruce W.

Abstract

Author(s): Jörg Kämper (corresponding author) [1]; Regine Kahmann (corresponding author) [1]; Michael Bölker (corresponding author) [2]; Li-Jun Ma [3]; Thomas Brefort [1]; Barry J. Saville [4, 27]; Flora Banuett [5]; [...]

Published
2006
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2. Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae

Author

Galagan, James E., Calvo, Sarah E., Cuomo, Christina, Ma, Li-Jun, Wortman, Jennifer R., Batzoglou, Serafim, Lee, Su-In, Başturkmen, Meray, Spevak, Christina C., Clutterbuck, John, Kapitonov, Vladimir, Jurka, Jerzy, Scazzocchio, Claudio, Farman, Mark, Butler, Jonathan, Purcell, Seth, Harris, Steve, Braus, Gerhard H., Draht, Oliver, Busch, Silke, D'Enfert, Christophe, Bouchier, Christiane, Goldman, Gustavo H., Bell-Pedersen, Deborah, Griffiths-Jones, Sam, Doonan, John H., Yu, Jaehyuk, Vienken, Kay, Pain, Arnab, Freitag, Michael, Selker, Eric U., Archer, David B., Penalva, Miguel A., Oakley, Berl R., Momany, Michelle, Tanaka, Toshihiro, Kumagai, Toshitaka, Asai, Kiyoshi, Machida, Masayuki, Nierman, William C., Denning, David W., Caddick, Mark, Hynes, Michael, Paoletti, Mathieu, Fischer, Reinhard, Miller, Bruce, Dyer, Paul, Sachs, Matthew S., Osmani, Stephen A., and Birren, Bruce W.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): James E. Galagan (corresponding author) [1]; Sarah E. Calvo [1]; Christina Cuomo [1]; Li-Jun Ma [1]; Jennifer R. Wortman [2]; Serafim Batzoglou [3]; Su-In Lee [3]; Meray Baştürkmen [4]; [...]

Published
2005
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3. The genome sequence of the rice blast fungus Magnaporthe grisea

Author

Dean, Ralph A., Talbot, Nicholas J., Ebbole, Daniel J., Farman, Mark L., Mitchell, Thomas K., Orbach, Marc J., Thon, Michael, Kulkarni, Resham, Xu, Jin-Rong, Pan, Huaqin, Read, Nick D., Lee, Yong-Hwan, Carbone, Ignazio, Brown, Doug, Oh, Yeon Yee, Donofrio, Nicole, Jeong, Jun Seop, Soanes, Darren M., Djonovic, Slavica, Kolomiets, Elena, Rehmeyer, Cathryn, Li, Weixi, Harding, Michael, Kim, Soonok, Lebrun, Marc-Henri, Bohnert, Heidi, Coughlan, Sean, Butler, Jonathan, Calvo, Sarah, Ma, Li-Jun, Nicol, Robert, Purcell, Seth, Nusbaum, Chad, Galagan, James E., and Birren, Bruce W.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Ralph A. Dean (corresponding author) [1]; Nicholas J. Talbot [2]; Daniel J. Ebbole [3]; Mark L. Farman [4]; Thomas K. Mitchell [1]; Marc J. Orbach [5]; Michael Thon [3]; [...]

Published
2005
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4. The genome sequence of the filamentous fungus Neurospora crassa

Author

Galagan, James E., Calvo, Sarah E., Borkovich, Katherine A., Selker, Eric U., Read, Nick D., Jaffe, David, FitzHugh, William, Ma, Li-Jun, Smirnov, Serge, Purcell, Seth, Rehman, Bushra, Elkins, Timothy, Engels, Reinhard, Wang, Shunguang, Nielsen, Cydney B., Butler, Jonathan, Endrizzi, Matthew, Qui, Dayong, Ianakiev, Peter, Bell-Pedersen, Deborah, Nelson, Mary Anne, Werner-Washburne, Margaret, Selitrennikoff, Claude P., Kinsey, John A., Braun, Edward L., Zelter, Alex, Schulte, Ulrich, Kothe, Gregory O., Jedd, Gregory, Mewes, Werner, Staben, Chuck, Marcotte, Edward, Greenberg, David, Roy, Alice, Foley, Karen, Naylor, Jerome, Stange-Thomann, Nicole, Barrett, Robert, Gnerre, Sante, Kamal, Michael, Kamvysselis, Manolis, Mauceli, Evan, Bielke, Cord, Rudd, Stephen, Frishman, Dmitrij, Krystofova, Svetlana, Rasmussen, Carolyn, Metzenberg, Robert L., Perkins, David D., Kroken, Scott, Cogoni, Carlo, Macino, Giuseppe, Catcheside, David, Li, Weixi, Pratt, Robert J., Osmani, Stephen A., DeSouza, Colin P. C., Glass, Louise, Orbach, Marc J., Berglund, J. Andrew, Voelker, Rodger, Yarden, Oded, Plamann, Michael, Seiler, Stephan, Dunlap, Jay, Radford, Alan, Aramayo, Rodolfo, Natvig, Donald O., Alex, Lisa A., Mannhaupt, Gertrud, Ebbole, Daniel J., Freitag, Michael, Paulsen, Ian, Sachs, Matthew S., Lander, Eric S., Nusbaum, Chad, and Birren, Bruce

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): James E. Galagan (corresponding author) [1]; Sarah E. Calvo [1]; Katherine A. Borkovich [2]; Eric U. Selker [3]; Nick D. Read [4]; David Jaffe [1]; William FitzHugh [5]; Li-Jun [...]

Published
2003
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5. GeNets: a unified web platform for network-based genomic analyses

Author

Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Li, Taibo, Regev, Aviv, Kim, April, Rosenbluh, Joseph, Horn, Heiko, Greenfeld, Liraz, An, David, Zimmer, Andrew, Liberzon, Arthur, Bistline, Jon, Natoli, Ted, Li, Yang, Tsherniak, Aviad, Narayan, Rajiv, Subramanian, Aravind, Liefeld, Ted, Wong, Bang, Thompson, Dawn, Calvo, Sarah, Carr, Steve, Boehm, Jesse, Jaffe, Jake, Mesirov, Jill, Hacohen, Nir, Lage, Kasper, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Li, Taibo, Regev, Aviv, Kim, April, Rosenbluh, Joseph, Horn, Heiko, Greenfeld, Liraz, An, David, Zimmer, Andrew, Liberzon, Arthur, Bistline, Jon, Natoli, Ted, Li, Yang, Tsherniak, Aviad, Narayan, Rajiv, Subramanian, Aravind, Liefeld, Ted, Wong, Bang, Thompson, Dawn, Calvo, Sarah, Carr, Steve, Boehm, Jesse, Jaffe, Jake, Mesirov, Jill, Hacohen, Nir, and Lage, Kasper

Abstract

Functional genomics networks are widely used to identify unexpected pathway relationships in large genomic datasets. However, it is challenging to compare the signal-to-noise ratios of different networks and to identify the optimal network with which to interpret a particular genetic dataset. We present GeNets, a platform in which users can train a machine-learning model (Quack) to carry out these comparisons and execute, store, and share analyses of genetic and RNA-sequencing datasets.

Published
2018

6. Comparative RNA editing in autistic and neurotypical cerebella

Author

Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Brown, Emery N., Eran, A., Li, J. B., Vatalaro, K., McCarthy, J., Rahimov, F., Collins, C., Markianos, K., Margulies, David M., Calvo, Sarah E., Kohane, Isaac, Kunkel, Louis M., Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Brown, Emery N., Eran, A., Li, J. B., Vatalaro, K., McCarthy, J., Rahimov, F., Collins, C., Markianos, K., Margulies, David M., Calvo, Sarah E., Kohane, Isaac, and Kunkel, Louis M.

Abstract

Adenosine-to-inosine (A-to-I) RNA editing is a neurodevelopmentally regulated epigenetic modification shown to modulate complex behavior in animals. Little is known about human A-to-I editing, but it is thought to constitute one of many molecular mechanisms connecting environmental stimuli and behavioral outputs. Thus, comprehensive exploration of A-to-I RNA editing in human brains may shed light on gene–environment interactions underlying complex behavior in health and disease. Synaptic function is a main target of A-to-I editing, which can selectively recode key amino acids in synaptic genes, directly altering synaptic strength and duration in response to environmental signals. Here, we performed a high-resolution survey of synaptic A-to-I RNA editing in a human population, and examined how it varies in autism, a neurodevelopmental disorder in which synaptic abnormalities are a common finding. Using ultra-deep (>1000 × ) sequencing, we quantified the levels of A-to-I editing of 10 synaptic genes in postmortem cerebella from 14 neurotypical and 11 autistic individuals. A high dynamic range of editing levels was detected across individuals and editing sites, from 99.6% to below detection limits. In most sites, the extreme ends of the population editing distributions were individuals with autism. Editing was correlated with isoform usage, clusters of correlated sites were identified, and differential editing patterns examined. Finally, a dysfunctional form of the editing enzyme adenosine deaminase acting on RNA B1 was found more commonly in postmortem cerebella from individuals with autism. These results provide a population-level, high-resolution view of A-to-I RNA editing in human cerebella and suggest that A-to-I editing of synaptic genes may be informative for assessing the epigenetic risk for autism., Nancy Lurie Marks Family Foundation, F. Hoffmann-La Roche & Co. (Applied Science Sequencing Grant Program), Autism Speaks (Organization), Simons Foundation, National Institutes of Health (U.S.) (Grant 1R01MH085143-01)

Published
2014

7. Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis

Author

National Human Genome Research Institute (US), Bayer, National Institutes of Health (US), Federal Ministry of Education and Research (Germany), Max Planck Society, Natural Sciences and Engineering Research Council of Canada, Canada Foundation for Innovation, Consejo Nacional de Humanidades, Ciencias y Tecnologías (México), Alexander von Humboldt Foundation, European Commission, Kämper, Jörg, Kahmann, Regine, Bölker, Michael, Ma, Li-Jun, Brefort, Thomas, Saville, Barry J., Banuett, Flora, Kronstad, James W., Gold, Scott E., Müller, Olaf, Perlin, Michael H., Wösten, Han A. B., Vries, Ronald de, Ruiz-Herrera, José, Reynaga-Peña, Cristina G., Snetselaar, Karen, McCann, Michael, Pérez-Martín, José, Feldbrügge, Michael, Basse, Christoph W., Steinberg, Gero, Ibeas, Jose I., Holloman, William K., Guzman, Plinio, Farman, Mark, Stajich, Jason E., Sentandreu, Rafael, González-Prieto, Juan M., Kennell, John C., Molina Delgado, Lázaro, Schirawski, Jan, Mendoza-Mendoza, Artemio, Greilinger, Doris, Münch, Karin, Rössel, Nicole, Scherer, Mario, Vraneš, Miroslav, Ladendorf, Oliver, Vincon, Volker, Fuchs, Uta, Sandrock, Björn, Meng, Shaowu, Ho, Eric C. H., Cahill, Matt J., Boyce, Kylie J., Klose, Jana, Klosterman, Steven J., Deelstra, Heine J., Ortiz-Castellanos, Lucila, Li, Weixi, Sanchez-Alonso, Patricia, Schreier, Peter H., Häuser-Hahn, Isolde, Vaupel, Martin, Koopmann, Edda, Friedrich, Gabi, Voss, Hartmut, Schlüter, Thomas, Margolis, Jonathan, Platt, Darren, Swimmer, Candace, Gnirke, Andreas, Chen, Feng, Vysotskaia, Valentina, Mannhaupt, Gertrud, Güldener, Ulrich, Münsterkötter, Martin, Haase, Dirk, Oesterheld, Matthias, Mewes, Hans-Werner, Mauceli, Evan W., DeCaprio, David, Wade, Claire M., Butler, Jonathan, Young, Sarah, Jaffe, David B., Calvo, Sarah, Nusbaum, Chad, Galagan, James, Birren, Bruce W., National Human Genome Research Institute (US), Bayer, National Institutes of Health (US), Federal Ministry of Education and Research (Germany), Max Planck Society, Natural Sciences and Engineering Research Council of Canada, Canada Foundation for Innovation, Consejo Nacional de Humanidades, Ciencias y Tecnologías (México), Alexander von Humboldt Foundation, European Commission, Kämper, Jörg, Kahmann, Regine, Bölker, Michael, Ma, Li-Jun, Brefort, Thomas, Saville, Barry J., Banuett, Flora, Kronstad, James W., Gold, Scott E., Müller, Olaf, Perlin, Michael H., Wösten, Han A. B., Vries, Ronald de, Ruiz-Herrera, José, Reynaga-Peña, Cristina G., Snetselaar, Karen, McCann, Michael, Pérez-Martín, José, Feldbrügge, Michael, Basse, Christoph W., Steinberg, Gero, Ibeas, Jose I., Holloman, William K., Guzman, Plinio, Farman, Mark, Stajich, Jason E., Sentandreu, Rafael, González-Prieto, Juan M., Kennell, John C., Molina Delgado, Lázaro, Schirawski, Jan, Mendoza-Mendoza, Artemio, Greilinger, Doris, Münch, Karin, Rössel, Nicole, Scherer, Mario, Vraneš, Miroslav, Ladendorf, Oliver, Vincon, Volker, Fuchs, Uta, Sandrock, Björn, Meng, Shaowu, Ho, Eric C. H., Cahill, Matt J., Boyce, Kylie J., Klose, Jana, Klosterman, Steven J., Deelstra, Heine J., Ortiz-Castellanos, Lucila, Li, Weixi, Sanchez-Alonso, Patricia, Schreier, Peter H., Häuser-Hahn, Isolde, Vaupel, Martin, Koopmann, Edda, Friedrich, Gabi, Voss, Hartmut, Schlüter, Thomas, Margolis, Jonathan, Platt, Darren, Swimmer, Candace, Gnirke, Andreas, Chen, Feng, Vysotskaia, Valentina, Mannhaupt, Gertrud, Güldener, Ulrich, Münsterkötter, Martin, Haase, Dirk, Oesterheld, Matthias, Mewes, Hans-Werner, Mauceli, Evan W., DeCaprio, David, Wade, Claire M., Butler, Jonathan, Young, Sarah, Jaffe, David B., Calvo, Sarah, Nusbaum, Chad, Galagan, James, and Birren, Bruce W.

Abstract

Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U. maydis belongs to the group of biotrophic parasites (the smuts) that depend on living tissue for proliferation and development. Here we report the genome sequence for a member of this economically important group of biotrophic fungi. The 20.5-million-base U. maydis genome assembly contains 6,902 predicted protein-encoding genes and lacks pathogenicity signatures found in the genomes of aggressive pathogenic fungi, for example a battery of cell-wall-degrading enzymes. However, we detected unexpected genomic features responsible for the pathogenicity of this organism. Specifically, we found 12 clusters of genes encoding small secreted proteins with unknown function. A significant fraction of these genes exists in small gene families. Expression analysis showed that most of the genes contained in these clusters are regulated together and induced in infected tissue. Deletion of individual clusters altered the virulence of U. maydis in five cases, ranging from a complete lack of symptoms to hypervirulence. Despite years of research into the mechanism of pathogenicity in U. maydis, no 'true' virulence factors had been previously identified. Thus, the discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi. Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens. ©2006 Nature Publishing Group.

Published
2006

9. Nuclear genetic control of mtDNA copy number and heteroplasmy in humans.

Author

Gupta R, Kanai M, Durham TJ, Tsuo K, McCoy JG, Kotrys AV, Zhou W, Chinnery PF, Karczewski KJ, Calvo SE, Neale BM, and Mootha VK

Subjects
Aged, Humans, Genome-Wide Association Study, Alleles, Polymorphism, Single Nucleotide, INDEL Mutation, G-Quadruplexes, DNA Copy Number Variations genetics, DNA, Mitochondrial genetics, Heteroplasmy genetics, Mitochondria genetics, Cell Nucleus genetics
Abstract

Mitochondrial DNA (mtDNA) is a maternally inherited, high-copy-number genome required for oxidative phosphorylation 1 . Heteroplasmy refers to the presence of a mixture of mtDNA alleles in an individual and has been associated with disease and ageing. Mechanisms underlying common variation in human heteroplasmy, and the influence of the nuclear genome on this variation, remain insufficiently explored. Here we quantify mtDNA copy number (mtCN) and heteroplasmy using blood-derived whole-genome sequences from 274,832 individuals and perform genome-wide association studies to identify associated nuclear loci. Following blood cell composition correction, we find that mtCN declines linearly with age and is associated with variants at 92 nuclear loci. We observe that nearly everyone harbours heteroplasmic mtDNA variants obeying two principles: (1) heteroplasmic single nucleotide variants tend to arise somatically and accumulate sharply after the age of 70 years, whereas (2) heteroplasmic indels are maternally inherited as mixtures with relative levels associated with 42 nuclear loci involved in mtDNA replication, maintenance and novel pathways. These loci may act by conferring a replicative advantage to certain mtDNA alleles. As an illustrative example, we identify a length variant carried by more than 50% of humans at position chrM:302 within a G-quadruplex previously proposed to mediate mtDNA transcription/replication switching 2,3 . We find that this variant exerts cis-acting genetic control over mtDNA abundance and is itself associated in-trans with nuclear loci encoding machinery for this regulatory switch. Our study suggests that common variation in the nuclear genome can shape variation in mtCN and heteroplasmy dynamics across the human population., (© 2023. The Author(s).)

Published
2023
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